Background: Although gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract, they are very rare. This study evaluated clinical and histopathological characteristics of duodenal GISTs to identify factors useful in predicting prognosis for patients with these tumors. Methods: A retrospective study was performed on 20 patients who had undergone surgery between 1987 and 2009 for duodenal GISTs. Clinical, histopathological, and immunohistochemical data were evaluated. Survival analyses were conducted using Kaplan-Meier estimates. Results: In 12 patients (60%), duodenal GISTs were diagnosed incidentally. Eight cases (40%) were classified as high risk grade GISTs. Skeinoid fibers (SkF), which are eosinophilic globular hyaline deposits in the extracellular interstitium of the tumor, were found in 12 patients. Skeinoid fibers were not recognized in 8 cases, and these included 3 cases (37.5%) where tumors recurred after surgery and the patient died. Tumors without SkF were larger (81 ± 92 vs. 23 ± 8 mm, P < 0.001) and had a higher mitotic count (224.0 ± 336.6 vs. 0.0 ± 0.0 /50 high-power field, P < 0.001) than those with SkF. Survival time was shorter in patients with tumors lacking SkF (52.9 ± 50.7 vs. 108.9 ± 86.5 months, P = 0.019). Conclusions: We have identified clinical and histopathological characteristics that were useful in predicting the prognosis of patients with duodenal GISTs. In this study, 60% of the tumors were found incidentally, SkF were not recognized in tumors from 40% of patients, and all cases of post-operative tumor recurrence and death occurred in this subgroup of patients.